Results obtained during the current project period included the distribution and actions of thyrotropin-releasing hormone (TRH) and gonadotropin releaseing hormone (GnRH) in the rat central nervous system, and kinetic characterization of TRH enzymatic degradation by rat hypothalamic cytosol. We studied the neuropharmacological regulation of TSH secretion in the intact rat. Clinical investigations concerning the potential role of prolactin (HPr) in the abnormal osmoregulation of diabetes mellitus, and anterior pituitary secretion of TSH, HPr and HGH in patients with anorexia nervosa were completed. We propose to extend ongoing studies of TRH in man, the whole rat, isolated rat hypothalami and rat adenohyophyses in vitro. Rat and human TSH, HPr,TRH, thyroxine and triiodothyronine will be determined by specific radioimmunoassays. High specific activity tritiated TRH and TRH affinity chromatography will be deployed to examine TRH biosynthesis in neural structures. We have set the following goals for the forthcoming period: To study the content and distribution of TRH and GnRH in the human central nervous system. To examine TRH concentrations in human peripheral blood in acromegaly, diabetes mellitus, and idiopathic hypopituitarism associated with tertiary hypothyroidism, and to study the mechanism of TRH biosynthesis in vitro, emphasizing potential synthetic capability of extrahypothalamic CNS loci. BIBLIOGRAPHIC REFERENCES: Wilber, J.F.: Pathogenic, diagnostic, and therapeutic considerations for abnormal states of anterior pituitary function in man. Proc. First Conference on Neuroendocrine Integration. Raven Press, 1975. Montoya, E.M., Siebel, M.J., Wilber, J.F.: Studies of TRH secretory physiology in the rat by immunoassay. Endocrinol 96:1413, 1975.